e23226 Background: The rising cost and complexity of cancer care has generated interest from clinicians, healthcare institutions, and payors in creating decision-making tools to help provide consistent, high-quality, and cost-effective care. In accordance with national best practices, the Sidney Kimmel Cancer Center (SKCC) at Thomas Jefferson University Hospital began using system-based clinical pathways (Elsevier’s ClinicalPath™) in August 2019. We hypothesized that regardless of pathway utilization, our treatment decisions by subspecialists would align with clinical pathway algorithms. Methods: Chemotherapy orders for breast, genitourinary (GU), and gastrointestinal (GI) cancers between August 1, 2019 and December 31, 2022 at SKCC were identified via database review. Those ordered outside ClinicalPath were selected for chart review to identify characteristics including disease stage, line of treatment, cycles administered, and treatment response. Orders were compared to contemporaneous versions of ClinicalPath to assess if they were on- or off-pathway. Finally, off-pathway treatments were compared to the NCCN guidelines to determine if they were consistent with the national standard of care. Results: 1670 breast, GU, and GI chemotherapy ordering encounters were identified. Of these, only 105 (6.3%) were ordered outside of the clinical pathways tool and underwent chart review. 41 (39%) treatments agreed with ClinicalPath recommendations despite being ordered outside this system, and 87 (82.2%) were aligned with national guidelines. Treatment of higher stage diseases was more commonly ordered outside of ClinicalPath, with 67.7% having stage 4 disease. Of the orders, alignment with ClinicalPath decreased by stage (57.1% stage 1 vs 36.6% stage 4) and further lines of therapy (48.8% first line vs 25.0% fourth line and beyond). Discordance with national guidelines also correlated with progressive lines of therapy, though not with increasing stage. Conclusions: 93.7% of breast, GU, and GI chemotherapy orders at our institution were entered in ClinicalPath. Often, a goal of staying “on-pathway” is 80%. Of those ordered without ClinicalPath, many agreed with the ClinicalPath recommendation and more than 80% agreed with national guidelines. Differences in pathway and guideline adherence by stage and line of therapy may reflect the complexity of treatment decisions in advanced disease and suggest difficulty capturing these nuances in ClinicalPath. While only a minority of treatment decisions are made outside of ClinicalPath, those decisions largely agree with national guidelines. At a large academic center with oncology subspecialists, further investigation is needed to better understand the additional value of widespread adoption of clinical pathway tools.